Currently, the majority of therapeutic and diagnostic agents are administered to patients systemically. Unfortunately, current delivery methods can have several disadvantages including reduced efficacy of therapeutics as well as side effects due to, for example, drug activation at non-target sites in a patient. In an effort to address some of these drawbacks, targeting delivery of nanoparticles associated with diagnostic and therapeutic agents presents a promising new mode of drug delivery.
Under certain circumstances, however, the nanoparticles can be rejected by a patient's immune system and processed before the nanoparticle can reach a target for delivery of a drug. To address these problems, surfaces of nanoparticles can be modified. For example, nanoparticles, such as liposomes, are commonly modified to incorporate polyethylene glycol (PEG) groups on their surface to enhance in vivo performance. Generally, there are two common approaches employed to achieve liposomal PEG modification. One approach includes combining lipid-PEG molecules to form liposomal formulations under mechanical means, e.g., extrusion. In another approach, liposomes can be preassembled and subsequently treated with a properly disposed PEG-lipid under conditions where the lipid can insert in the liposome bilayer, thereby forming a liposome with PEG attached to the liposome surface.
While there have been some recent advancements in developing targeted drug delivery methods, there is still a need for further improvements. For example, current approaches for modifying nanoparticles provide only a limited number of modifications that can be made to a nanoparticle. The present invention addresses these and other needs.